What is Goodpasture syndrome?

Key points

Goodpasture syndrome is a very rare autoimmune disorder in which your body mistakenly makes antibodies that attack the lungs and kidneys
It occurs more often in people aged 20 to 30 or older than age 60 years. It is more common in men
It can be fatal if not quickly diagnosed and treated
If the kidneys fail, dialysis or kidney transplant may be needed
Treatment involves immunosuppression and plasma exchange. The aim is to prevent your immune system from destroying kidney and lung tissue.

So. What is Goodpasture syndrome?

Goodpasture syndrome is a group of usually serious acute illnesses that affects the lungs and kidneys. It is also called anti-glomerular basement membrane (anti-GBM) disease, as its caused by antibodies to the glomerular basement membrane (GBM). The antibodies can also attack the basement membranes in the lungs.

It is an autoimmune disorder. It can present as haemoptysis (lung bleeding) or AKI – usually a combination of these symptoms. It can also occasionally cause glomerulonephritis (10-20%) or pulmonary disease (10%) alone.

As it can affect the kidneys or lungs, it can be called a pulmonary-renal syndrome (PRS; see below).

Normally, the immune system makes antibodies to fight off germs. But with Goodpasture syndrome, the immune system mistakenly makes antibodies that attack the lungs and kidneys.

This condition can quickly progress to an inflammation of the kidneys (glomerulonephritis) and acute kidney injury (AKI). It can be fatal if not quickly diagnosed and treated.

In most cases, this disease does not cause lasting damage to the lungs, if it is diagnosed rapidly. But kidney damage may be long-lasting (CKD leading to ESRF – i.e. dialysis and/or a kidney transplant), especially if the diagnosis or treatment is delayed.

Goodpasture syndrome was named after Ernest Goodpasture, who first described this disorder in 1919.

Who gets Goodpasture syndrome?

This disease most often occurs in people ages 20 to 30 or those older than age 60. But it can occur at any age. The condition can occur in children, but this is extremely rare. It is largely a disease of white people.

Fortunately it is very rare in adults as well, affecting 1 in 1 million people per year.

What causes Goodpasture syndrome?

Doctors do not know the precise cause of this disease. It can run in families, so genetics may play a role. It is more likely to be due to a combination of factors.

Goodpasture syndrome appears to result from environmental factors (see below) in a person with a genetic predisposition. At this point, a triggering stimulus has not been identified for the development of AGBM antibodies.

However, certain human leukocyte antigen (HLA) subtypes (proteins in your cells) increase your genetic susceptibility to Goodpasture syndrome – most notably HLA-DR15.

Environmental factors include:

Drugs, such as alemtuzumab that causes lymphocyte-depletion
Cocaine
Infections, such as influenza A2
Smoking
Exposure to metal dust, organic solvents, or hydrocarbons (e.g. methane or propane)
Extracorporeal shock wave lithotripsy.

Whatever the cause(s), the AGBM autoantibody is to the alpha-3 chain of type IV collagen. This type of collagen is principally found in the basement membranes of alveoli and glomeruli.

What are the symptoms of Goodpasture syndrome?

These are the most common symptoms of Goodpasture syndrome:

Non-specific symptoms, including nausea and fatigue
Cough
Haemoptysis (coughing up blood)
Shortness of breath – due to fluid overload (pulmonary oedema) and/or lung bleeding (pulmonary haemorrhage)
There can be blood (haematuria), and mild-moderate levels of protein in the urine (proteinuria) – shown on urinary dipstick or laboratory testing.

The symptoms of Goodpasture syndrome occur in other causes of PRSs (e.g. systemic lupus erythematosus (SLE) and ANCA-positive vasculitis) or other conditions (e.g. pulmonary oedema due to heart failure). This is why the diagnosis is often missed or delayed (and its very rare).

How is Goodpasture syndrome diagnosed?

Your doctor take a medical history and do a physical examination. Then the following tests are required.

Blood tests. These will usually show an AKI
Immunology blood tests. Anti-glomerular basement antibodies (AGBM) are found. Anti-cytoplasmic antibodies (ANCA) may be present as well. These are called ‘double positive’ patients. ANCA is more usually linked to ANCA-positive vasculitis which is a similar disease to Goodpasture syndrome
Urine tests. These include a urinary dipstick, ACR and MSU. Protein may be found in the urine along with red and white blood cells, and groups of cells and cellular material stuck together (granular casts)
Kidney biopsy. A rapidly progressive glomerulonephritis (RPGN) is characteristic on renal biopsy. It causes 10-20% of cases of RPGN

A typical kidney biopsy in Goodpasture syndrome. This shows ‘crescents’ around the glomeruli which are a feature of all RPGNs.

This is another biopsy technique called immunofluorescence (IF) that shows AGBM antibodies

Other biopsies. In some situations (e.g. lack of kidney involvement) a bronchoscopy (looking into the lungs with a telescope) and lung biopsy may be necessary
Chest x-ray and/or CT chest. These look for pulmonary oedema and/or haemorrhage.

Typical CXR in Goodpasture syndrome. There are many other causes of this appearance

What is the treatment for Goodpasture syndrome?

Treatment includes immunosuppression. These stop your immune system from making antibodies. They can also make you at greater risk for infections. So you may also be prescribed antibiotics. It includes:

Steroids – they are used to decrease inflammation and tissue damage. They can be given IV (as methylprednisolone) or orally (as prednisolone)
Cyclosphosphamide – a very strong immunosuppressant drug that can be given IV or orally
Other immunosuppressants – such as ciclosporin, mycophenolate and rituximab have also been used
Plasma exchange – this is a process, a bit like dialysis, in which blood plasma is removed, cleaned of harmful antibodies, and then returned to your body.

Other treatments may be required

Other drugs – you may also be given medication to control fluid overload and high blood pressure
Dialysis – usually in the short-term may be required
Ventilation – if the lung problems are severe, ventilation (being paralysed and put on a breathing machine) on ICU may be needed – again usually in the short-term.

What can I do to help myself?

Not smoking and avoidance of secondary smoke is very important.

Prognosis (outlook)

Untreated, Goodpasture syndrome is usually fatal. Long-term outcome is related to the degree of reduced function of the kidneys at diagnosis. Patients requiring urgent dialysis, and those with > 50% crescents (see above) in the kidney biopsy (who often will require dialysis), usually live for < 2 years unless kidney transplantation is done.

Haemoptysis is a good prognostic sign because it leads to earlier detection; the minority of patients who are ANCA-positive (i.e. have two auto-antibodies) respond better to treatment.

Goodpasture syndrome is usually a ‘one-hit’ disease. In other words, once treated and if renal function returns to normal, immunosuppression can eventually be withdrawn. This is different to ANCA-positive vasculitis, and other causes of a PRS, where recurrence is common, and immunosuppression is not normally withdrawn.

Relapse occurs in a small number of patients, and is linked to continued tobacco use and respiratory infection.

In patients with ESRF who receive kidney transplantation, the disease can recur in the transplant.

Terminology

Goodpasture syndrome is used by some to describe any cause of a PRS, leading to AKI and pulmonary haemorrhage. Whereas Goodpasture disease is a PRS when AGBM antibodies are present. And ‘Anti-GBM disease‘ is used to describe any patient with typical autoantibodies, with any clinical features (including no renal involvement).

Summary

We have described What is Goodpasture syndrome. It is a very serious disease where rapid diagnosis and treatment is important. We hope it has been helpful.

Other resource

This a review article: DeVrieze, 2022.

https://www.youtube.com/watch?app=desktop&v=Vko4lYWgwrs

Last Reviewed on 23 May 2024